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Biomedical subjects

A Kettrup

Publications and source records attributed to A Kettrup.

At least 109 records · Page 6Linked to original sources
PubMed1998

Influence of an aquatic humic acid on the bioconcentration of selected compounds in Daphnia magna.

Several chemicals covering a wide range of octanol-water partition coefficients were assayed for their bioconcentration in Daphnia magna in the presence of an aquatic humic acid. Assuming the properties of the humic acid used were similar to those known for organic matter from soils, the influence of the aquatic humic acid on physicochemical moderation of bioconcentration could not be demonstrated experimentally in a log Kow range of the chemicals between 2 and 6. Thus, the lipophilic character of the aquatic humic acid and the related effect of solubilization of the chemicals in the aqueous phase are much less than expected. This result is confirmed by determining the octanol-water partition coefficient of the aquatic humic acid. Comparing this value with log Kow values of humic acids of terrestrial origin, it can be clearly demonstrated that the lipophilicity of the aquatic humic acid is lower by a factor of 50.

1-Octanol↗
PubMed1998

Establishment of a simple cleanup procedure and bioassay for determining 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents of environmental samples.

The study was aimed at establishing a bioassay for the determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents (TEQs) in environmental samples. Specifically, development of a rapid cleanup procedure adapted to the needs of the bioassay and simplification of the measurement of its endpoint, the induction of 7-ethoxyresorufin O-deethylase (EROD) in rat H4IIEC3/T hepatoma cells, were desired. The results indicate that a single "sandwich" column suffices to remove substances that may interfere with the bioassay from extracts of various environmental matrices such as sewage sludge, compost, soil, sediment, fly ash, tissue filter dust, and fire residue. The cumbersome conventional in vitro assay for EROD activity on cells exposed to the test material in culture plates could readily be replaced by a simple assay on intact cells grown and treated in 96-well microtiter plates. TEQ values obtained from the bioassays were consistently higher than those derived from chemical analysis of dibenzo-p-dioxins/furans and biphenyls by a factor of 1.5-3.0 depending on the matrix used. The results indicate that this bioassay, which combines a simple cleanup and a rapid procedure for measuring biological effects, offers a cost- and time-effective alternative to chemical analysis when screening large numbers of samples from complex environmental matrices.

Animals↗
PubMed1998

Glutathione S-transferase activity in aquatic macrophytes with emphasis on habitat dependence.

Glutathione S-transferase activity of both the microsomal and soluble fractions was determined in a variety of aquatic macrophytes. The examined enzyme extract was prepared from a combination of leaves and shoots. Four different model substrates were used. The highest conjugation rate was obtained for 1-iodo-2,4-dinitrobenzene, followed by 1-chloro-2,4-dinitrobenzene, p-nitrobenzoyl chloride, and 1,2-dichloro-4-nitrobenzene. Comparison of several samples of Nuphar lutea L. from two different lake areas revealed increased glutathione S-transferase activity in plants from the site contaminated with polyaromatic hydrocarbons.

Environment↗
PubMed1998

Subchronic/chronic toxicity of a mixture of four chlorinated dibenzo-p-dioxins in rats. I. Design, general observations, hematology,and liver concentrations.

Groups of 20 male and 20 female rats were administered five different doses of a mixture of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8-pentaCDD (PCDD), 1,2,3,4,7,8-hexaCDD (HxCDD), and 1,2,3,4,6,7,8-heptaCDD (HpCDD). Doses were selected based on relative potency factors derived from acute toxicity data and a previous subchronic study with HpCDD. The mixture was constituted such that each of the congeners contributed one fourth to total toxic equivalency. Total doses were divided into four daily loading doses and six biweekly maintenance doses. The highest total dose for males was 17.5 microg/kg of TCDD, 87.5 microg/kg of PCDD, 350 microg/kg of HxCDD, and 2500 microg/kg of HpCDD. Positive controls were administered PCDD (350 microg/kg) or HxCDD (1400 microg/kg). Females were given 1.5 times lower doses than males. The dosing period was 13 weeks, after which half of the rats were necropsied and the rest provided with an off-dose period of another 13 weeks. Liver concentrations as determined by GC-MS reflected the doses administered. Body weight gain was dose-dependently reduced throughout the study. Mortality rates at the end of the off-dose period were 80 and 60% for the two highest dosages (mixture) in males and 70 and 10% for females. Clinical signs and necropsy findings suggested that the cause of death was related to wasting, hemorrhage, and anemia. Prothrombin times were prolonged and platelet counts were decreased in some rats receiving high doses. This study provides in vivo support for the validity of the assumption of additive toxicity of CDDs as currently used in the toxicity equivalency factor approach to assess the toxicity of mixtures of CDDs.

Administration, Oral↗
PubMed1998

Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in the sediments of an Italian drinking water reservoir.

The concentration of 9 polychlorinated biphenyls (PCB 28, 52, 101, 151, 153, 170, 180, 183 and 194) and of 6 micropollutants commonly classified as organochlorine pesticides, or OCPs (alpha-HCH, beta-HCH, gamma-HCH, p,p'-DDT, p,p'-DDE and p,p'-DDD), was determined in 22 sediment samples of lake Simbirizzi, an artificial reservoir supplying drinking water to the city of Cagliari (Sardinia, Italy). The quantification was performed by analysing purified sediment extract with HRGC-ECD. The average concentrations proved to be relatively low. In the case of p,p'-DDE, the contaminant with the highest concentration, a mean value of 0.84 ppb (micrograms/kg d.m.) was found. These relatively low concentrations and the comparison with data relating to other lakes suggest that, as far as PCBs and the majority of OCPs are considered, atmospheric inputs are likely to be the main source of contamination. Only for lindane (gamma-HCH) it is possible to assume a contribution from agricultural activities. The presence of its isomers (alpha-HCH and beta-HCH) was attributed to natural occurring reactions of the gamma-form.

Agriculture↗
PubMed1997

Considerations on genetic and environmental factors that contribute to resistance or sensitivity of mammals including humans to toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Part 1: Genetic factors affecting the toxicity of TCDD.

The marked species differences in short-term toxicity (30-day LD50) of ca. 10,000 (LD50: guinea pigs ca. 1 microgram/kg body wt and Han/Wistar Kuopio rats more than 9600 micrograms/kg body wt) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the central issues of the controversies that have developed on the validity of risk assessment strategies for TCDD and related compounds. One of the most challenging issues that toxicologists face today is the identification of genes that contribute to or are responsible for increased resistance or sensitivity to TCDD and related compounds. It is assumed that most, if not all, toxic effects of TCDD are mediated more or less through the binding affinity to the Ah receptor. This hypothesis was extended and tries to explain the differences in sensitivity/resistance of animals including humans to TCDD by their total fat (lipid) content. In this respect the gene or genes which is or are responsible for obesity of mammals including humans are of great interest. An obvious linear positive logarithmic relationship between the oral 30-day LD50 (microgram/kg) of TCDD in different species and strains of mammals and their total body fat content (TBF%) was found: log LD50 = 5.30 x log (TBF)-3.22, or LD50 = 0.000603 x (TBF)5.30. By means of this regression the toxicity of TCDD in mammals including humans of different age and/or body weight can be predicted if their total body fat content is known. Examples of single-gene and polygenic disease models in different mammals, such as nonobese diabetic, diabetic, viable yellow, obese, and fat mice, as well as transgenic mice, and other suitable animal models, such as fatty Zucker rats, Han/Wistar (Kuopio) rats, and minipigs, are discussed, and predicted LD50 values of TCDD in these animals and humans are presented.

Animals↗
PubMed1997

Subchronic/chronic toxicity of 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) in rats. Part I. Design, general observations, hematology, and liver concentrations.

Groups of 20 male and 20 female adult Sprague-Dawley rats were given five different doses of 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD). Total doses for males and females (30.9/18.5, 370/222, 2222/1333, 6667/4000, and 10000/6000 microg/kg) were divided into four daily loading doses and six biweekly maintenance doses. Positive controls were administered 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD, total dose 70/41.9 microg/kg). Liver concentrations, as determined by GC/MS, reflected quite accurately the calculated dose ratios. The dosing period was 13 weeks, after which half of the rats were necropsied and the rest provided with an off-dose period of another 13 weeks. Body weight gain was dose-dependently reduced throughout the study. Mortality occurred dose-dependently, starting on Day 22 and continuing until the end of the off-dose period. Mortality rates at the end of the off-dose period were 90 and 40% for males and 60 and 10% for females in the two highest dose groups. Clinical signs and necropsy findings suggested that the cause of death was related to wasting (early deaths), gastrointestinal and nasal hemorrhage (between Days 64 and 126), or anemia (late deaths, after Day 111). Prothrombin times were prolonged intermittently, mainly at the highest dose of HpCDD. Platelet counts were dose-dependently decreased at the two highest doses of HpCDD and in the TCDD-treated group. This study demonstrates that the relative potency derived from acute toxicity studies is the same as that observed in this subchronic/chronic toxicity study of HpCDD and TCDD, confirming the validity of 0.007 as the toxic equivalency factor (TEF) for HpCDD, which is in good agreement with the international TEF of 0.01.

Administration, Oral↗
PubMed1997

Levels of chlorinated hydrocarbons (CHC) in breams (Abramis brama) from the river Elbe (a contribution to the Federal Environmental Specimen Bank).

The levels of chlorinated hydrocarbon (CHC) contaminants in muscle and liver tissues of bream (Abramis brama) along the river Elbe were monitored during 1991, 1993 and 1994. Especially fish from the eastern sampling sites (Prossen, Dresden) has been heavily contaminated by HCB, OCS, DDT-metabolites and PCBs. In 1991, the concentrations of OCS, DDE and PCBs decreased significantly by 65, 65 and 51%, respectively, between Dresden and Vockerode and did not change very much from Vockerode downstream to Cumlosen. Elevated HCH levels were found in Aken, Barby and Heinrichsberg. An increasing temporal pattern during this period was found for HCB, OCS and DDE in Prossen.

Animals↗
PubMed1997

PCBs and PCDD/Fs in lake sediments of Grosser Arbersee, Bavarian Forest, South Germany.

Despite their environmental importance, there are still relatively few historical studies of the environmental occurrence of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), especially in middle Europe. Trends in PCBs and PCDD/Fs were, therefore, assessed in lake sediments of the Grosser Arbersee over the past 130 years (1860-1990). Ballschmiter-PCB concentrations (congeners # 28, 52, 101, 138, 153, 180) increased between 1946 and 1972 from 4.2 to 32.0 microg kg(-1) dry wt, but have since decreased to 25.6 microg kg(-1) dry wt. High chlorinated PCB congeners reached their maxima earlier (1968-1972) than low chlorinated congeners (1985-1991). These trends were consistent with patterns expected from the production and use of PCBs and their precursors. PCDD/F concentrations increased between 1950 from 0.6 microg kg(-1) dry wt to 2.3 microg kg(-1) dry wt in 1977, falling to 1.7 microg kg(-1) dry wt by 1993. PCDF concentrations exceeded those of PCDD until 1968, but afterwards PCDDs (especially OCDD) were predominant. These patterns suggest that domestic heating and waste combustion were the most likely sources, but pollution from local industries, such as metal smelting and glass production, might also have been involved. The data provide a valuable case study from central Europe which confirms the overall declining trends of PCB and PCDD/F contamination shown elsewhere.

Journal Article↗
PubMed1996

Preliminary experiments for the analysis of tetrahydrotetrols of benz[a]anthracene and benzo[a]pyrene derived from their hemoglobin adducts using a coupled-column high-performance liquid chromatographic system.

Improved technologies for the detection of polycyclic aromatic hydrocarbon adducts are required for human biomonitoring. Therefore, a coupled-column high-performance liquid chromatographic method, with system-integrated sample processing, has been developed and its applicability for determination of tetrahydrotetrols of polycyclic aromatic hydrocarbons in acid hydrolysates of human hemoglobin has been investigated. A novel column-switching technique applying "thermotransfer' is used to separate tetrahydrotetrols of benzo[a]pyrene and benz[a]anthracene more efficiently. Derivatives of polycyclic aromatic hydrocarbons from blood hydrolysates are concentrated on a pre-column and then transferred to the analytical column by applying an electrical current to heat the solvent eluting the pre-column. This method allows for rapid and quantitative transfer of the analytes from the pre-column to the analytical column, after HPLC-integrated sample processing.

Benz(a)Anthracenes↗
PubMed1996

Computer-assisted peak recognition for polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) in environmental samples.

A software has been developed for the peak recognition of 136 polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) after high resolution gas chromatography coupled with mass spectrometry (HRGC/HRMS). Based on the retention times of (13)C labelled 2,3,7,8-substituted PCDD/F internal standards, the retention times of all PCDD and PCDF can be calibrated automatically and accurately. Therefore, it is very convenient to identify the peaks by comparing the retention of samples and the calibrated retention times of their chromatograms. Hence, this approach is very significant because it is impossible to obtain always a standard chromatogram and PCDD/F analysis are very expensive and time consuming. The calibration results can be transferred to Excel for calculation. The approach is a first step to store costly and environmentally relevant data for future application.

Journal Article↗
PubMed1996

Quality criteria for the isotope dilution method with HRGC/MS.

The isotope dilution method is characterized by the use of appropiately labelled standard compounds in conjunction with mass spectrometry coupled to chromatographic systems. Although the isotope dilution method seems to be a simple procedure, some quality criteria for sample preparation, measurement and quantification have to be considered. Furthermore, archiving and documentation of analysis data as well as the use of reference materials to validate the analysis method are important with regard to European standard regulations for quality assurance. In view of this background and the increasing application tendency to environmental problems, essential quality critera for the isotope dilution method are presented and discussed, with special respect to sample extraction, separation performance and sensitivity. Also the quantification procedures are summarized.

Journal Article↗
PubMed1996

Flocculation of humic substances with metal ions as followed by capillary zone electrophoresis.

Humic and fulvic acids from various sources have been shown to give different electropherograms by capillary zone electrophoresis (CZE), depending on the pH of the electrolyte. This CZE work is extended here through investigations involving the titration of humic and fulvic acids with Fe(III) and Cu(II) cations. As increasing amounts of these cations were added to the humic substances (HUS), flocculation of metal-humic complexes occurred. This is believed to be caused by binding of the metal cations with negative carboxyl and phenolic sites on the HUS, resulting in a decrease of the repulsive forces that keep the HUS in a conformation more suitable for water solubility. The flocculated complexes were separated from the supernatant by centrifugation, and the supernatants were characterized as to total organic carbon (TOC) content, molecular weight (MW) using gel permeation chromatography, and average electrophoretic mobility (AEM) using CZE. The extent of flocculation correlated with both TOC and quantitative CZE measurements. The MW of the HUS remaining in solution actually decreased, presumably because of precipitation of larger molecules as they became insoluble because of reactions with the metals. Humic acids showed total precipitation of TOC with both metals at a concentration equivalent to their measured acidity. CZE demonstrated that certain fulvic acid fractions (low molecular weight phenolic acids) remained in solution even at high metal concentrations. In summary, changes in electrophoretic behavior of the soluble HUS could be related to changes in charge-to-mass ratios (charge densities) of both humic and fulvic acids with increasing metal cation concentration (neutralization). The copper treated HUS showed changes in their electrophoretic behavior even at low metal concentrations before flocculation, whereas the iron treated HUS flocculated uniformally over the range of added iron without significant changes in AEM. Thus these changes in CZE patterns illustrate different specific binding sites of the HUS for each metal.

Journal Article↗
PubMed1996

Determination of trace metal ions Co, Cu, Mo, Mn, Fe, Ti, V in reference river water and reference seawater samples by inductively coupled plasma emission spectrometry combined with the third phase preconcentration.

A combination of DAM-SCN(-) third phase extraction and inductively coupled plasma emission spectrometry (ICP-AES) is used for the determination of trace metal ions in a river water and a seawater reference material. An implementation of the third phase extraction prior to ICP-AES allows a preconcentration of trace elements (Co, Cu, Mn, Fe, V, Ti, Mn) by a factor ranging from 33 to 45. A complete separation of these elements is accomplished from matrices, normally affecting the excitation characteristics of ICP and suppressing the elemental signals severely. Different factors, including pH of the solutions, amounts of reagents, matrix effects, have been investigated and optimized. Under the conditions selected, the limits of determination have been in the range of 0.02 to 0.6 microg/L. The system has been successfully applied to the determination of Cu, Mn, V in the reference river water SLRS-3 and Mo in the reference seawater NASS-3. The results were in a good agreement with the certified values.

Journal Article↗
PubMed1996

Determination of aromatic hydrocarbons in air using diffusion denuders.

The results of a study to evaluate a recently developed denuder sampling system for the determination of aromatic hydrocarbons in air are presented. Denuders of different lengths were tested in laboratory experiments by means of dynamically generated test gases at conditions similar to those at workplaces. Uptake rates, adsorption capacities as well as desorption efficiencies were measured at different sampling parameters. The influence of air humidity on the adsorption behaviour was determined. Finally, the suitability of the system for outdoor air investigations was checked. The denuders were very suitable for the determination of aromatic hydrocarbons in workplace air; the general feasibility to investigate outdoor air samples was demonstrated.

Journal Article↗
PubMed1996

A pond mesocosm study to determine direct and indirect effects of lindane on a natural zooplankton community.

We assessed the threshold concentrations for toxic effects by lindane on a zooplankton community using mesocosms in a natural pond. Enclosures (1000 litres) were treated to give mean concentrations of 0, 2, 6, 12, 18, 24, and 50 microg litre(-1) over a test period of 39 days. Larvae of the phantom midge Chaoborus flavicans showed a high susceptibility to lindane and were virtually eliminated from enclosures with > or =12 microg litre(-1) 4 days after application. Populations of cyclopoid nauplii (Eucyclops serrulatus) were reduced at a lindane concentration of 2 microg litre(-1) and showed high mortality after 11 days exposure to > or =6 g litre(-1). No lindane-induced effects could be seen in the cladoceran species Daphnia longispina and Chydorus sphaericus. Rotifer species were probably not directly affected by lindane; however loss of the principal predator Chaoborus was accompanied by an increase in the numbers of Asplanchna priodonta. A simultaneous decrease in Keratella quadrata possibly reflected predation since its decline showed no dose-response relationship with lindane and it is among the major prey of Asplanchna. Such complex secondary effects, occurring through trophic interactions between a predator and two co-occurring prey, would not have been predicted from single-species toxicity tests. These, and effects on cyclopoid populations that occurred predominantly through the mortality of nauplii, demonstrate the value of toxicological studies on natural communities. We conclude that a combination of laboratory and field investigations, coupled with mono-species and community assessments, provide the best route for understanding the effects of toxicants such as lindane for regulatory purposes.

Journal Article↗
PubMed1995

Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. IV. Determination of liver concentrations.

Groups of male Sprague-Dawley rats were administered orally the following chlorinated dibenzo-p-dioxins (CDDs) in corn oil/acetone (95/5; v/v): 30-60 micrograms/kg 2,3,7,8-tetrachlorodibenzo-dioxin (tetra-CDD), 160-270 micrograms/kg1,2,3,7,8-pentachlorodibenzo-p-dioxins (penta-CDD), 630-1249 micrograms/kg 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD) and 5000-8000 micrograms/kg 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD) or a mixture of the four homologues such that each was present in the mixture at one quarter of its dose as a single compound. Animals were killed at 2 and 8 days after dosing. Livers were immediately removed, and aliquots frozen in liquid nitrogen. Storage occurred at -80 degrees C until further use. About 0.2 g of each lyophilized rat liver was extracted, the extract purified by column chromatography and analyzed by GC/MS for CDD content. Results obtained suggest that the absorption of CDDs after oral administration decreases in the order of tetra-CDD > or = penta-CDD > hexa-CDD > hepta-CDD, indicating that the dose was an incomplete surrogate of exposure in parts I-III of this publication series (Stahl et al. 1992; Weber et al. 1992a,b). Moreover, data also support the notion that the pharmacokinetics of CDD mixtures at high doses are somewhat different from those expected based on single compound exposures. Our findings suggest that the intrinsic relative potency in terms of toxic equivalents (TEQ) of the higher chlorinated homologues is slightly greater (about a factor of 2) than suggested by Stahl et al.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗